Cannabis and other illicit drug use in epilepsy patients.

BACKGROUND AND PURPOSE: This study aimed to assess the prevalence of illicit drug use among epilepsy patients and its effects on the disease. METHODS: We systematically interviewed epilepsy outpatients at a tertiary epilepsy clinic. Predictors for active cannabis use were analysed with a logistic regression model. RESULTS: Overall, 310 subjects were enrolled; 63 (20.3%) reported consuming cannabis after epilepsy was diagnosed, and 16 (5.2%) used other illicit drugs. Active cannabis use was predicted by sex (male) [odds ratio (OR) 5.342, 95% confidence interval (95% CI) 1.416-20.153] and age (OR 0.956, 95% CI 0.919-0.994). Cannabis consumption mostly did not affect epilepsy (84.1%). Seizure worsening was observed with frequent illicit (non-cannabis) drug use in 80% of cases. CONCLUSIONS: Cannabis use does not seem to affect epilepsy; however, frequent use of other drugs increases seizure risk.

High frequency of intrathecal immunoglobulin synthesis in epilepsy so far classified cryptogenic.

BACKGROUND AND PURPOSE: The influence of the immune system on seizures and epileptogenesis has been increasingly considered, in particular the role of autoantibodies. In this study, we aimed to determine the frequency of intrathecal antibody synthesis in the cerebrospinal fluid (CSF) compartment of patients with epilepsy. METHODS: In a retrospective cohort study trial in a university hospital neurology department, 164 well-characterized patients with different etiologies of seizures and epilepsies, and 77 control patients were included. RESULTS: CSF-specific immunoglobulin (IgG, IgM and IgA) synthesis was significantly (P < 0.0001) more frequent in patients with epilepsy (34.1%) compared with age- and sex-matched controls (2.6%). The highest incidence of intrathecal Ig synthesis was detected in patients with encephalitis-related acute symptomatic seizures (86.7%), but also in patients with focal epilepsy so far classified cryptogenic (45.2%). Antibody synthesis was not related to the number of CSF white blood cells. CONCLUSIONS: Humoral immune activation in the CSF compartment was detected in one-third of patients with epilepsy, besides acute symptomatic seizures particularly frequent in cryptogenic epilepsy--an etiology so far defined as not having a detectable cause. Systematic prospective clinical and experimental trials are required to identify antigenic targets and select appropriate patients for which immunotherapy might offer new causal therapeutic options.

Dopaminergic activation excites rat lateral habenular neurons in vivo.

The lateral habenular complex (LHb) of the epithalamus is part of a dorsal diencephalic conduction system connecting basal forebrain with regulatory midbrain nuclei. The LHb has been implicated in the regulation of ascending monoaminergic transmission, particularly midbrain dopaminergic neuronal activity. Here, we have investigated whether the LHb in turn is subject to dopaminergic modulation. Alterations in spontaneous neuronal activity within the LHb following systemic application of dopaminergic drugs have been examined in anesthetized rats using extracellular single unit recordings. The administration of apomorphine (2 mg/kg) resulted in an excitation of individual LHb neurons. On average, the spontaneous action potential firing of the LHb neurons was increased by 39%. However, the apomorphine effect showed marked topographic differences within the LHb. Particularly, a small subset of neurons in the lateral division of the LHb, which was localized within the oval subnucleus, showed an apomorphine-mediated increase in discharge frequency by 96%. In contrast, spontaneous discharge of neurons within other areas of the lateral division was not modified. Likewise, within the medial division of the LHb, a region that preferentially receives projections from dopaminergic midbrain nuclei, the majority of neurons failed to show apomorphine-mediated alterations in action potential firing. However, within the superior subnucleus of this division, an area with yet unclear afferent supply, spontaneous neuronal firing was enhanced by 56%. The apomorphine-mediated excitation of LHb neurons was antagonized by coapplication of haloperidol (2 mg/kg), which alone did not alter spontaneous action potential firing of individual LHb neurons. The present study demonstrates that spontaneous activity of distinct subsets of neurons within the LHb is strongly enhanced by systemic activation of dopaminergic receptors. Despite the small sample size, the data suggest that this dopaminergic modulation shows a topographic specificity. Therefore, the results support the hypothesis of a functional subnuclear organization of the rat habenular complex.

Cellular and subcellular rat brain spermidine synthase expression patterns suggest region-specific roles for polyamines, including cerebellar pre-synaptic function.

In the brain, the polyamines spermidine (Spd) and spermine (Spm) serve highly specific functions by interacting with various ion channel receptors intimately involved with synaptic signaling. Both, glial cells and neurons contain Spd/Spm, but release and uptake mechanisms could re-distribute polyamines between cell types. The cellular and subcellular localization of polyamine biosynthetic enzymes may therefore offer a more appropriate tool to identify local sources of enhanced Spd/Spm synthesis, which may be related with specific roles in neuronal circuits and synaptic function. A recently characterized antibody against Spd synthase was therefore used to screen the rat brain for compartment-specific peaks in enzyme expression. The resulting labeling pattern indicated a clearly heterogeneous expression predominantly localized to neurons and neuropil. The highest levels of Spd synthase expression were detected in the accumbens nucleus, taenia tecta, cerebellar cortex, cerebral cortical layer I, hippocampus, hypothalamus, mesencephalic raphe nuclei, central and lateral amygdala, and the circumventricular organs. Besides a diffuse labeling of the neuropil in several brain areas, the distinct labeling of mossy fiber terminals in the cerebellar cortex directly indicated a synaptic role for Spd synthesis. Electron microscopy revealed a preferential distribution of the immunosignal in synaptic vesicle containing areas. A pre-synaptic localization was also observed in parallel and climbing fiber terminals. Electrophysiological recordings in acute cerebellar slices revealed a Spd-induced block of evoked extracellular field potentials resulting from mossy fiber stimulation in a dose-dependent manner.